The complement system serves as an important source of chemotactic factors for tumor cells. Preliminary evidence indicates that a fragmentation product of C5a is the tumor cell chemotactic factor for tumor cells. The proposed studies will define the nature of the C5 derived chemotactic factor for tumor cells. The cleavage peptide from C5a will be isolated and characterized. Studies will be initiated to define receptor binding of the chemotactic factor to tumor cells. The following chemotactic factor induced changes on tumor cells will be assessed: transmembrane ionic fluxes, membrane depolarization, intracellular changes in CAMP and CGMP, and the possible role of methyltransferase. Concomitant functional changes (pinocytosis, protein synthesis, transport) will also be studied. The biological activity of the C5 chemotactic factor and the bone resorption chemotactic factor for tumor cells will be studied in vivo for the ability to induce peritoneal and intrapulmonary metastases. Finally, the influence of C5 on biological behavior of malignant cells, the growth and the rate of metastases of malignant tumors in C5 deficient and C5 sufficient mice will be probed.